End-stage renal disease (ESRD) is a late-onset multifactorial disease that primarily occurs in a subset of patients with diabetes mellitus, hypertension or chronic glomerulonephritis. ESRD incidence is rising with an annual mortality of about 20% in incident cases. ESRD clusters in families and familial aggregation is a more powerful predictor of whether an individual with diabetes mellitus, hypertension or chronic glomerulonephritis will develop ESRD. However, no particular genetic mechanism responsible for the renal function damage that ultimately leads to ESRD has yet been identified. We are recruiting 150 affected sib pairs concordant for ESRD and Type 2 diabetes, and 100 sib pairs discordant for ESRD (but concordant for Type 2 diabetes mellitus) and 200 additional family members from hemodialysis, peritoneal dialysis and transplant centers as part of a study to identify genetic risk factors for ESRD. We are collecting extensive family history and medical history, as related to ESRD, on all members of the family recruited into the study. Blood will be obtained from consenting family members. Data will be analyzed using model-free linkage analysis. This dataset is expected to be complex and we will have to subdivide the data by race/ethnicity for analysis. We anticipate that this study will lead to identification of gene(s) for ESRD. [unreadable]